NRG Oncology (GOG/RTOG) Current GCIG Studies in the NRG 1. NRG 278 - - PowerPoint PPT Presentation

Current GCIG Studies in the NRG 1. NRG 278 2. NRG 263 (KGOG 0801) 3. NRG 0724 (RTOG) 4. NRG 0274 (ANZGOG OUTBACK) 5. AIM2CERV/GOG 3009 6. NRG GY006 7. NRG 270 (GROINSS-V II) 8. NRG 279 9. GOG 3016

• 10. GOG 2024

NRG Oncology (GOG/RTOG)

GOG 278

Study Chair: A Covens

PI = AL COVENS N = 220 Enrollment to date = 172 Primary Endpoint = QOL

Stage IA2-IB2: Positive nodes, parametrial extension, positive margins after radical hysterectomy

NRG/RTOG 0724

R A N D O M I Z E Pelvic Radiation and Weekly cisplatin (CCRT) Pelvic Radiation and Weekly cisplatin (CCRT) followed by carboplatin + Paclitaxel x 4 cycles

PI = Anuja Jhingran N = 285 Enrollment to date = 184 Primary Endpoint = DFS

NRG GY006

Newly diagnosed uterine cervix cancer

• Squamous
• Adenosquamous
• Adenocarcinoma

Clinical stage bulky (> 5 cm) IB2, or Clinical stage II, IIIB, or IVA followed by Negative para-aortic nodal staging by PET/CT Stratify para-aortic node-negative patients by:

• a. Age (≤ 45 years or > 45 years)
• b. Performance status (0, 1, or 2)
• c. Intensity Modulated Radiation Therapy (yes or no)
• d. Stage (≤ clinical stage II, or ≥ clinical stage III)

RANDOMIZE

Arm 1:

• Radiation
• Cisplatin

Arm 2:

• Radiation
• Cisplatin
• Triapine

Radiation: 45 Gy / 25 fractions of 1.8 Gy + 5.4 Gy / 3 fraction parametrium boost + 40 Gy LDR or 30 Gy HDR brachytherapy Cisplatin: X1 weekly cisplatin 40 mg/m2 (maximum 70 mg) days 2, 9, 16, 23, 30 of radiation (5 total infusions; a sixth administration on day 36 is permissible at the treating physician’s discretion.) Triapine: X3 weekly 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (Triapine) 25 mg/m2 (maximum 50 mg) days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, 33 of radiation (15 total infusions)

PI = TREY LEATH MD N = 188 Enrollment to date = 150 Primary Endpoint = RFS

NTO-1151- Triapine: Small molecule chelator – inhibits ribonuclease reductase Will transition into phase 3 study N=348

6

AIM2CERV / GOG 3009

** 3 years of Lm surveillance from time of last dose to include 90 days of antibiotics **

PI = THOMAS HERZOG MD N = 455 Enrollment to date = 99 Primary Endpoint = RFS

• Recurrent,

persistent, and/or metastatic cervical cancer

• Progressed

within 6 months

• f the last dose
• f platinum

GOG-3016 (R (R2810-ONC-1676 ) )

R A N D O M I Z E

REGN2810 350 mg Q3W, for up to 96 weeks Physicians choice chemotherapy

PI = Krishnansu S. Tewari, MD N = 436 Primary Endpoint = OS Enrollment = 160

Pemetrexed 500 mg/m2 Q3W Topotecan 1 mg/m2 daily for 5 days, Q21 days Irinotecan 100 mg/m2 days 1, 8, 15, & 22, followed by 2 weeks rest (6-week cycle) Vinorelbine 30 mg/m2 days 1 & 8, Q21 days Gemcitabine 1000 mg/m2 on days 1 & 8, Q21 days REGN2810, a fully human monoclonal antibody against programmed death-1 (PD-1)

Empower Cervical 1

Empower Cervical 1:

R2810-ONC-1676/GOG-3016/ENGOT CX9/GEICO 72-C

GCIG IG Meeting

Ana Oaknin, MD PhD Head of Gynecologic Cancer Program. Vall d´Hebron Institute of Oncology(VHIO). Vall d´Hebron University Hospital. GEICO Vice-Chairman Barcelona, Spain

Empower Cervical 1 Review

• 1. Participant Groups / Countries
• 2. Sample Size: Recruitment update
• 3. ENGOT Groups Study Timelines

BGOG (Belgium) PGOG (Poland) MaNGO (Italy) HeCOG (Greece) MITO (Italy) NCRI (UK) ENGOT Lead Group: GEICO (Spain), PI Dr. Ana Oaknin

Empower Cervical 1 Review ENGOT Participant Groups / Countries

Empower Cervical 1 Review

ENGOT Groups’ Participation

▪ GEICO: 10 sites, 40 patients PI: Dr. Ana Oaknin ▪ PGOG: 03 sites, 12 patients PI: Dr. Radoslaw Madry* ▪ BGOG: 06 sites, 24 patients PI: Dr. Ignace Vergote ▪ MaNGO: 05 sites, 20 patients PI: Dr. Domenica Lorusso* ▪ MITO: 06 sites, 24 patients PI: Dr. Domenica Lorusso ▪ HeCOG: 06 sites, 24 patients PI: Dr. Flora Zagouri ▪ NCRI: 06 sites, 24 patients PI: Dr. Azmat Sadozye 42 sites, 168 patients

*Italy( MITO&MANGO)will have a common PI. * PGOG’s PI needS to confirm his participation in the Study

Empower Cervical 1 Review ENGOT Groups Study Timelines

GROUP Submission Planned SIV-FPI Planned GEICO

• Dr. Ana Oaknin

Amendment for news sites addition planned for Nov 2018 1st SIV-FPI for the new sites planned in January / February 2019 BGOG

• Dr. Ignace Vergote

Submission planned for November 2018 1st SIV-FPI planned in January / February 2019 MaNGO

• Dr. Domenica Lorusso

Submission planned for November 2018 1st SIV-FPI planned in February / March2019 MITO

• Dr. Domenica Lorusso

Submission planned for November 2018 1st SIV-FPI planned in February / March2019 HeCOG

• Dr. Flora Zagouri

Submission planned for January 2019 1st SIV planned in April / May 2019 NCRI

• Dr. Azmat Sadozye

Submission already done: 31Aug2018 1st SIV-FPI planned in January / February 2019

GOG 279

PROTOCOL GOG-0279 A PHASE II TRIAL EVALUATING CISPLATIN (NSC #119875) AND GEMCITABINE (NSC # 613327) CONCURRENT WITH INTENSITY-MODULATED RADIATION THERAPY (IMRT) IN THE TREATMENT OF LOCALLY ADVANCED SQUAMOUS CELL CARCINOMA OF THE VULVA NCI Version Date: 11/02/2012 Includes Revision #1

POINTS: PER CAPITA - 20 MEMBERSHIP – 3 .

’ ’

Study Chair: NS Horowitz MD Target 52 evaluable patients Enrollment to date = 40

GOG 2024 ENGOT-cx6/ENGOT-cx8

• Tisotumab vedotin is an Antibody-Drug

Conjugate (ADC) composed of a human mAb specific for Tissue Factor (TF= TROMBOPLASTIN), a protease-cleavable linker, and the microtubule disrupting agent MMAE1,a,b

• TF is a transmembrane protein that is

the main physiological initiator of coagulation and is involved in angiogenesis, cell adhesion, motility, and cell survival3

• TF is aberrantly expressed in a broad

range of solid tumours, including cervical cancer, and is associated with poor prognosis4,5

ADC=antibody-drug conjugate; mAb=monoclonal antibody; MMAE=monomethyl auristatin E.

aTissue factor is known as TF, CD142, and thromboplastin. bMMAE-based ADC technology was licensed from Seattle Genetics, Inc., in a license and collaboration agreement.

• 1. Breij EC et al. Cancer Res. 2014;74(4):1214-1226. 2. De Goeij BE et al. Mol Cancer Ther. 2015;14(5):1130-1140. 3. Chu AJ. Int J Inflam. 2011;2011. doi: 10.4061/2011/367284.
• 4. Förster Y et al. Clin Chim Acta. 2006;364(1-2):12-21. 5. Cocco E et al. BMC Cancer. 2011;11:263.
• 1. Binding to TF
• 2. Internalization of

tisotumab vedotin

• 3. Intracellular trafficking to

the lysosomes

• 4. Enzymatic degradation of

tisotumab vedotin, intracellular release of MMAE

• 5. MMAE induces cell death

by microtubule disruption

• 6. Release of MMAE in tumour

microenvironment induces bystander killing of neighbouring cancer cells

Mechanism of action Tisotumab Vedotin

Activating Trials – status update

Phase I expansion in ≥ 2nd line recurrent Cxca (Vergote et al ESMO 2017) 32% OF PATIENTS WITH RECURRENT/ADVANCED CERVICAL CANCER ACHIEVED RESPONSE WITH TISOTUMAB VEDOTIN

CI=confidence interval; CR=complete response; CT=computed tomography; DCR=disease control rate; ORR=overall response rate; PD=progressive disease; PR=partial response; RECIST=Response Evaluation Criteria in Solid Tumors; SD=stable disease.

aTwo patients were withdrawn prior to CT scan, and so are not represented in the graph. bPD due to new lesion at same scan. cClinical benefit was defined as the DCR rate, the proportion of patients

who achieved a CR, PR, or SD after 12 weeks. dResponse was as assessed by investigators using standard RECIST 1.1 criteria. eOne of which is still ongoing. Data cutoff date July 24, 2017.

• 50% (17 of 34 patients; 95% CI, 35%-65%) clinical benefit after 12 wks (DCR)c,d
• 32% (11 of 34 patients; 95% CI, 17%-50%) response (ORR)d

− 8 PR, confirmed − 3 PR, unconfirmede PR

b b b b

Change at first scan Maximum reduction N=34a Confirmed response Best Percent Change From Baseline, %

STUDY DESIGN GOG 3024 / ENGOT-cx6: Tisotumab Vedotin in Previously treated recurrent or metastatic cervical cancer

• Tisotumab vedotin

(TV) 2.0 mg/kg 1Q3W

• Imaging every 6

weeks first 30 weeks and every 12 weeks thereafter.

• Imaging assessed

locally (by PI) and centrally (by IRC*).

Treatment

N ~ 100

• Continue TV treatment

until IRC verified PD or until pt. fulfils other treatment discontinuation criteria e.g. unacceptable adverse events.

• Pt. is followed up for

survival and new anti- cancer treatment until the

• pt. dies or until withdrawal

from the trial.

Design

Enrollment

1

Patients with recurrent or metastatic cervical cancer who have received at least

• ne prior line of

systemic therapy.

• Data obtained from central IRC review will be used in the analysis and reporting of trial

results.

*IRC: Independent review committee

ENGOT Model C Activating Trials – status update Enrollment = 18 as of Oct 15, 2018 (33 active sites)

Trial setting: Post radical hysterctomy cervical cancer, Intermediate risk, Stage I/IIA Study Design: Adjuvant RT vs CRT Sponsor(s): NCI-NRG Planned No. of patients: 360 Current accrual: 280 Revision: Update (11/2017): Based on the observed accrual rate through November 2017, power analysis and sample size calculations using the Gompertz model suggest that enrolling at least 342 eligible and evaluable patients will result in the required number of recurrences without any changes to the study operating characteristics. Assuming uniform accrual with 5% ineligible proportion estimated from this study, the targeted accrual is 360 patients expected to be met in 2020.

GOG263: RANDOMIZED CLINICAL TRIAL OF

ADJUVANT RADIATION VERSUS CHEMORADIATION IN INTERMEDIATE RISK, STAGE I/IIA CERVICAL CANCER TREATED WITH INITIAL RADICAL HYSTERECTOMY AND PELVIC LYMPHADENECTOMY

GOG263: RANDOMIZED CLINICAL TRIAL OF

ADJUVANT RADIATION VERSUS CHEMORADIATION IN INTERMEDIATE RISK, STAGE I/IIA CERVICAL CANCER TREATED WITH INITIAL RADICAL HYSTERECTOMY AND PELVIC LYMPHADENECTOMY

Cervical cancer

Stage I-IIA Radical hysterectomy+BPLND >2 of intermediate risk factors

Control Arm; Radiation therapy CRT Arm; Weekly CDDP 40mg/m2 concurrent to radiation Randomization

50 100 150 200 250 300 10-10 11-2 11-6 11-10 12-2 12-6 12-10 13-2 13-6 13-10 14-2 14-6 14-10 15-2 15-6 15-10 16-2 16-6 16-10 17-2 17-6 17-10 18-2 Golobal KGOG

Target 360 Accrual 291

GOG263: RANDOMIZED CLINICAL TRIAL OF

ADJUVANT RADIATION VERSUS CHEMORADIATION IN INTERMEDIATE RISK, STAGE I/IIA CERVICAL CANCER TREATED WITH INITIAL RADICAL HYSTERECTOMY AND PELVIC LYMPHADENECTOMY